The Craniofacial Developmental Molecular Biology Program will consist of investigators from the University of Southern California, Schools of Dentistry and Medicine who participate in a multi-disciplinary research team focused on investigations of craniofacial genetics and developmental biology. The faculty collaboration includes investigators from the USC Institute of Genetic Medicine, the USC Comprehensive Cancer Center and the USC Center for Craniofacial Molecular Biology. The overall Program theme will use molecular biology approaches to investigate fundamental mechanisms required for normal development of the craniofacial complex. These findings will be applicable to further the understanding of normal developmental regulation and the molecular etiology of craniofacial birth defects. The Craniofacial Developmental Molecular Biology Program will consist of five Research Projects and one Core Resource. Project 1 (Dr. Yang Chai), "Characterization of Genes Involved in the Specification of Tooth and Meckel's Cartilage Morphogenesis," will characterize the Smad- related intracellular signaling pathway that is activated during mandibular morphogenesis. Project 2 (Dr. Larry Kedes) "Co-Activators and Repressors of Muscle Transcription," will investigate the activity of Twist, p300/CBP and PCAF during the differentiation of muscle cells. Project 3 (Dr. Yi-Hsin Liu) "Genes Involved in Skull Suture Morphogenesis," will examine patters of gene expression unique to the cranial sutures that may be correlated with abnormal suture development resulting in craniosynostosis. Project 4 (Dr. Robert Maxon) "Function of MSX2 and Twist in Calvarial Morphogenesis," will examine the regulation and activation of interacting transcription factors Twist and Msx2 during bone cell commitment and differentiation. Project 5 (Dr. Charles Shuler) " Mechanisms of Epithelial-Mesenchymal Transformation during Palatogenesis," will investigate the molecular mechanism underlying the epithelial-mesenchymal transdifferentiation of the medial edge epithelium during palatal fusion. The activities of the Program will be supported by an Administrative Core that will provide support for purchasing, manuscript preparation, scheduling for seminars and collaborative research planning and financial management. The Program will benefit from the availability of several other established cores at the University of Southern California available to support the research activities of all the Projects. This program will continue a long-term series of collaborations that have provided an excellent scientific environment to advanced the understanding of the molecular mechanisms underling craniofacial development.